Candida glabratabinds to glycosylated and lectinic receptors on the coronary endothelial luminal membrane and inhibits flow sense and cardiac responses to agonists

2016 ◽  
Vol 310 (1) ◽  
pp. R24-R32 ◽  
Author(s):  
David Torres-Tirado ◽  
Maureen Knabb ◽  
Irene Castaño ◽  
Araceli Patrón-Soberano ◽  
Alejandro De Las Peñas ◽  
...  
Keyword(s):  
Left Ventricular Pressure ◽  
Coronary Perfusion Pressure ◽  
Left Ventricular ◽  
Host Cells ◽  
Coronary Perfusion ◽  
Type I ◽  
Cardiac Responses ◽  
Luminal Membrane ◽  
Opportunistic Fungal Pathogen ◽  
Av Delay

Candida glabrata (CG) is an opportunistic fungal pathogen that initiates infection by binding to host cells via specific lectin-like adhesin proteins. We have previously shown the importance of lectin-oligosaccharide binding in cardiac responses to flow and agonists. Because of the lectinic-oligosaccharide nature of CG binding, we tested the ability of CG to alter the agonist- and flow-induced changes in cardiac function in isolated perfused guinea pig hearts. Both transmission and scanning electron microscopy showed strong attachment of CG to the coronary endothelium, even after extensive washing. CG shifted the coronary flow vs. auricular-ventricular (AV) delay relationship upward, indicating that greater flow was required to achieve the same AV delay. This effect was completely reversed with mannose, partially reversed with galactose and N-acetylgalactosamine, but hyaluronan had no effect. Western blot analysis was used to determine binding of CG to isolated coronary endothelial luminal membrane (CELM) receptors, and the results indicate that flow-sensitive CELM receptors, ANG II type I, α-adrenergic 1A receptor, endothelin-2, and VCAM-1 bind to CG. In addition, CG inhibited agonist-induced effects of bradykinin, angiotensin, and phenylephrine on AV delay, coronary perfusion pressure, and left ventricular pressure. Mannose reversed the inhibitory effects of CG on the agonist responses. These results suggest that CG directly binds to flow-sensitive CELM receptors via lectinic-oligosaccharide interactions with mannose and disrupts the lectin-oligosaccharide binding necessary for flow-induced cardiac responses.

Contribution of extravascular compression to reduction of maximal coronary blood flow

1992 ◽  
Vol 262 (1) ◽  
pp. H68-H77
Author(s):  
F. L. Abel ◽  
R. R. Zhao ◽  
R. F. Bond
Keyword(s):  
Blood Flow ◽  
Coronary Blood Flow ◽  
Coronary Flow ◽  
Perfusion Pressure ◽  
Left Ventricular Pressure ◽  
Coronary Perfusion Pressure ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Coronary Perfusion ◽  
Storage Site

Effects of ventricular compression on maximally dilated left circumflex coronary blood flow were investigated in seven mongrel dogs under pentobarbital anesthesia. The left circumflex artery was perfused with the animals' own blood at a constant pressure (63 mmHg) while left ventricular pressure was experimentally altered. Adenosine was infused to produce maximal vasodilation, verified by the hyperemic response to coronary occlusion. Alterations of peak left ventricular pressure from 50 to 250 mmHg resulted in a linear decrease in total circumflex flow of 1.10 ml.min-1 x 100 g heart wt-1 for each 10 mmHg of peak ventricular to coronary perfusion pressure gradient; a 2.6% decrease from control levels. Similar slopes were obtained for systolic and diastolic flows as for total mean flow, implying equal compressive forces in systole as in diastole. Increases in left ventricular end-diastolic pressure accounted for 29% of the flow changes associated with an increase in peak ventricular pressure. Doubling circumferential wall tension had a minimal effect on total circumflex flow. When the slopes were extrapolated to zero, assuming linearity, a peak left ventricular pressure of 385 mmHg greater than coronary perfusion pressure would be required to reduce coronary flow to zero. The experiments were repeated in five additional animals but at different perfusion pressures from 40 to 160 mmHg. Higher perfusion pressures gave similar results but with even less effect of ventricular pressure on coronary flow or coronary conductance. These results argue for an active storage site for systolic arterial flow in the dilated coronary system.

Intramyocardial pressure gradients in working and nonworking isolated cat hearts

1994 ◽  
Vol 266 (3) ◽  
pp. H1233-H1241 ◽  
Author(s):  
L. S. Mihailescu ◽  
F. L. Abel
Keyword(s):  
Perfusion Pressure ◽  
Left Ventricular Pressure ◽  
Coronary Perfusion Pressure ◽  
Left Ventricular ◽  
Mechanical Resistance ◽  
Coronary Perfusion ◽  
Pressure Gradients ◽  
Intramyocardial Pressure ◽  
Krebs Henseleit Buffer ◽  
Transmural Gradient

This study presents an improved method for the measurement of intramyocardial pressure (IMP) using the servo-nulling mechanism. Glass micropipettes (20-24 microns OD) were used as transducers, coated to increase their mechanical resistance to breakage, and placed inside the left ventricular wall with a micropipette holder and manipulator. IMP was measured at the base of the left ventricle in working and nonworking isolated cat hearts that were perfused with Krebs-Henseleit buffer. In working hearts a transmural gradient of systolic IMP oriented from endocardium toward the epicardium was found; the endocardial values for systolic IMP were slightly higher than systolic left ventricular pressure (LVP), by 11-18%. Increases in afterload induced increases in IMP, without changing the systolic IMP-to-LVP ratio. In nonworking hearts with drained left ventricles, the systolic transmural gradient for IMP described for working hearts persisted, but at lower values, and was directly dependent on coronary perfusion pressure. Systolic IMP-to-LVP ratios were always > 1. The diastolic IMP of both working and nonworking hearts exhibited irregular transmural gradients. Our results support the view that generated systolic IMP is largely independent of LVP development.

Transmural distribution of blood flow during activation of coronary muscarinic receptors

1981 ◽  
Vol 240 (6) ◽  
pp. H941-H946 ◽  
Author(s):  
G. J. Gross ◽  
J. D. Buck ◽  
D. C. Warltier
Keyword(s):  
Blood Flow ◽  
Muscarinic Receptors ◽  
Left Ventricular Pressure ◽  
Coronary Perfusion Pressure ◽  
Left Ventricular ◽  
Tissue Blood Flow ◽  
Coronary Perfusion ◽  
Coronary Vasodilator ◽  
Blood Flow Ratio

The role of coronary muscarinic receptors in the distribution of transmural blood flow across the left ventricular wall of the working heart was studied in anesthetized open-chest dogs. Tissue blood flow in subepicardium, midmyocardium, and subendocardium was determined with radioactive microspheres before and during activation of muscarinic vasodilator receptors by intracoronary infusions of acetylcholine. Myocardial and coronary vascular beta-receptors were blocked by sotalol (2.0 mg/kg iv). Equivalent submaximal coronary vasodilator doses of acetylcholine and adenosine were compared for effects on transmural blood flow. Intracoronary infusions of acetylcholine (5.0 and 10.7 micrograms/min) produced a dose-related increase in the subendocardial-subepicardial blood flow ratio (endo/epi) from 1.07 to 1.32 and 1.57, respectively. A progressively larger decrease in coronary vascular resistance occurred in the subendocardium than midmyocardium or subepicardium following acetylcholine administration. In contrast, intracoronary administration of adenosine (54.4 micrograms/min) produced no change in endo/epi. Atropine effectively blocked acetylcholine-induced coronary vasodilation but not vasodilation produced by adenosine. Neither agent affected heart rate, left ventricular pressure, coronary perfusion pressure, or myocardial contractility. These results suggest that activation of muscarinic coronary vasodilator receptors redistributes blood flow preferentially to the subendocardium independent of cardiac mechanical influences.

Direct cardiac effects of vasopressin: role of V1- and V2-vasopressinergic receptors

1988 ◽  
Vol 255 (2) ◽  
pp. H261-H265 ◽  
Author(s):  
B. R. Walker ◽  
M. E. Childs ◽  
E. M. Adams
Keyword(s):  
Left Ventricular Pressure ◽  
Coronary Perfusion Pressure ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Coronary Perfusion ◽  
Cardiac Effects ◽  
Coronary Vasoconstriction ◽  
Langendorff Preparation ◽  
Wide Range ◽  
Male Wistar Rats

Experiments were performed to determine the possible direct effects of arginine vasopressin (AVP) on cardiac function in the nonworking Langendorff preparation. Hearts were isolated from male Wistar rats, and the coronary arteries were retrograde perfused at a constant rate through the aorta with a Krebs-Henseleit solution, which was continuously bubbled with 95% O2–5% CO2. The hearts were paced at 280 beats/min and measurements made of peak ventricular pressure (PVP), first derivative of left ventricular pressure (dP/dtmax), and coronary perfusion pressure (CPP). By maintaining constant coronary flow, the direct cardiac effects of AVP could be determined independent of changes in myocardial O2 delivery elicited by potential coronary vasoconstriction. Myocardial function was assessed at AVP concentrations of 0, 10, 25, 50, 100, 200, 400, and 500 pg/ml. Progressive coronary vasoconstriction was observed with increasing AVP concentration. In contrast, PVP and dP/dtmax increased at 50 and 100 pg/ml of AVP but fell at 400 and 500 pg/ml. The maximal PVP and dP/dtmax responses were at 50 pg/ml (+16 +/- 3 and +44 +/- 4%, respectively), whereas at 500 pg/ml both PVP and dP/dtmax were reduced below control (-30 +/- 4 and -34 +/- 5%, respectively). Pretreatment with the specific V1-vasopressinergic antagonist d(CH2)5Tyr(Me)AVP (40 ng/ml) totally blocked both the coronary vasoconstrictor and contractility responses to AVP. Furthermore, infusion of a specific V2-agonist was without effect even at high doses. These data suggest that although AVP causes dose-related coronary vasoconstriction over a wide range of AVP concentrations, the hormone may exert a positive inotropic effect at doses mimicking circulating levels encountered in a number of pathophysiological situations.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of freeze-dried red wine on cardiac function and ECG of the Langendorff-perfused rat heart

2014 ◽  
Vol 92 (2) ◽  
pp. 171-174 ◽  
Author(s):  
Antonella Ferrara ◽  
Fabio Fusi ◽  
Beatrice Gorelli ◽  
Giampietro Sgaragli ◽  
Simona Saponara
Keyword(s):  
Cardiac Function ◽  
Red Wine ◽  
Left Ventricular Pressure ◽  
Coronary Perfusion Pressure ◽  
Left Ventricular ◽  
Coronary Perfusion ◽  
Rat Hearts ◽  
Freeze Dried ◽  
High Concentrations ◽  
Vasodilating Activity

The effect of freeze-dried red wine (FDRW) on cardiac function and electrocardiogram (ECG) in Langendorff-isolated rat hearts was investigated. FDRW significantly decreased left ventricular pressure and coronary perfusion pressure, the latter being dependent on the activation of both phosphatidylinositol 3-kinase and eNOS. FDRW did not affect the QRS and QT interval in the ECG, although at 56 μg of gallic acid equivalents/mL, it prolonged PQ interval and induced a second-degree atrioventricular block in 3 out of 6 hearts. This is the first study demonstrating that at concentrations resembling a moderate consumption of red wine, FDRW exhibited negative inotropic and coronary vasodilating activity leaving unaltered ECG, whereas at very high concentrations, it induced arrhythmogenic effects.

scholarly journals Cardiac arrest complicating cardiogenic shock: from pathophysiological insights to Impella-assisted cardiopulmonary resuscitation in a pheochromocytoma-induced Takotsubo cardiomyopathy—a case report

2021 ◽  
Vol 5 (3) ◽  
Author(s):  
Filippo Zilio ◽  
Simone Muraglia ◽  
Roberto Bonmassari
Keyword(s):  
Cardiac Arrest ◽  
Cardiopulmonary Resuscitation ◽  
Left Ventricle ◽  
Cardiogenic Shock ◽  
Takotsubo Cardiomyopathy ◽  
Perfusion Pressure ◽  
Coronary Perfusion Pressure ◽  
Left Ventricular ◽  
Coronary Perfusion ◽  
Refractory Cardiac Arrest

Abstract Background A ‘catecholamine storm’ in a case of pheochromocytoma can lead to a transient left ventricular dysfunction similar to Takotsubo cardiomyopathy. A cardiogenic shock can thus develop, with high left ventricular end-diastolic pressure and a reduction in coronary perfusion pressure. This scenario can ultimately lead to a cardiac arrest, in which unloading the left ventricle with a peripheral left ventricular assist device (Impella®) could help in achieving the return of spontaneous circulation (ROSC). Case summary A patient affected by Takotsubo cardiomyopathy caused by a pheochromocytoma presented with cardiogenic shock that finally evolved into refractory cardiac arrest. Cardiopulmonary resuscitation was performed but ROSC was achieved only after Impella® placement. Discussion In the clinical scenario of Takotsubo cardiomyopathy due to pheochromocytoma, when cardiogenic shock develops treatment is difficult because exogenous catecholamines, required to maintain organ perfusion, could exacerbate hypertension and deteriorate the cardiomyopathy. Moreover, as the coronary perfusion pressure is critically reduced, refractory cardiac arrest could develop. Although veno-arterial extra-corporeal membrane oxygenation (va-ECMO) has been advocated as the treatment of choice for in-hospital refractory cardiac arrest, in the presence of left ventricular overload a device like Impella®, which carries fewer complications as compared to ECMO, could be effective in obtaining the ROSC by unloading the left ventricle.

Abstract 14109: Basic Life Support With Reperfusion Injury Protection Improves 24 Hour Survival Outcomes in a Porcine Model of Prolonged Cardiac Arrest

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Guillaume Debaty ◽  
Keith G Lurie ◽  
Anja Metzger ◽  
Michael Lick ◽  
Jason Bartos ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Reperfusion Injury ◽  
Basic Life Support ◽  
Life Support ◽  
Coronary Perfusion Pressure ◽  
Left Ventricular ◽  
Adverse Outcomes ◽  
Left Ventricular Ejection ◽  
Coronary Perfusion ◽  
Ventricular Ejection Fraction

Introduction: Ischemic postconditioning (PC) using 3 intentional short pauses at the start of cardiopulmonary resuscitation (CPR) improves outcomes after cardiac arrest in pigs when epinephrine (epi) is used before defibrillation. Hypothesis: Basic life support (BLS) with PC will protect against reperfusion injury and enhance 24 hour functional recovery in the absence of epi. Methods: Female pigs (n=46; wt ~ 40 kg) were anesthetized (isoflurane). PC was delivered using 3 cycles alternating between automated CPR for 20 sec and no CPR for 20 sec at the start of each protocol. Protocol A: After 12 minutes of ventricular fibrillation (VF), 28 pigs were randomized in 4 groups: A/ Standard CPR (SCPR), B/ active compression-decompression with an impedance threshold device (ACD-ITD), C/ SCPR+PC (SCPR+PC) and D/ ACD-ITD+PC. Protocol B: After 15 min of VF, 18 pigs were randomized to ACD-ITD CPR or ACD-ITD + PC. The BLS duration was 2.75 min in Protocol A and 5 min in Protocol B. Following BLS up to 3 shocks were delivered. Without return of spontaneous circulation (ROSC) CPR was resumed and epi (0.5 mg) and defibrillation delivered. The primary end point was the incidence of major adverse outcomes at 24 h (defined as death or coma, refractory seizures and cardio-respiratory distress leading to euthanasia). Hemodynamic parameters and left ventricular ejection fraction (LVEF) were also measured. Data are presented as mean ± standard error of mean. Results: Protocol A: ACD-ITD CPR + PC (group D) provided the highest coronary perfusion pressure after 3 min of BLS compared with the 3 other groups (28 ± 6, 35 ± 7, 23 ± 5 and 47 ± 7 for groups A, B, C, D respectively, p= 0.05 by ANOVA). ROSC with BLS was achieved in 0, 3, 0, and 3 pigs in groups A, B, C and D, respectively (p=0.22) with no significant differences in 24-hour survival between groups. Protocol B: Four hours post ROSC, LVEF was significantly higher with ACD-ITD+IPC vs ACD-ITD alone (52.5 ± 3% vs. 37.5 ± 6.6%, p = 0.045). There was a significantly lower incidence of major adverse outcomes 24 hr after ROSC with ACD-ITD+PC compared with ACD-ITD alone (Log-rank comparison, p=0.027). Conclusion: BLS using ACD-ITD + PC mitigates post resuscitation cardiac dysfunction and facilitates neurological recovery after prolonged untreated VF in pigs.

Activation of PKC decreases myocardial O2consumption and increases contractile efficiency in rats

2001 ◽  
Vol 281 (5) ◽  
pp. H2191-H2197 ◽  
Author(s):  
Teruo Noguchi ◽  
Zengyi Chen ◽  
Stephen P. Bell ◽  
Lori Nyland ◽  
Martin M. LeWinter
Keyword(s):  
Perfusion Pressure ◽  
Diastolic Pressure ◽  
Coronary Perfusion Pressure ◽  
Left Ventricular ◽  
Regulatory Proteins ◽  
Basal Metabolism ◽  
Coronary Perfusion ◽  
Kinase C ◽  
Rat Hearts ◽  
Pkc Activation

The effect of protein kinase C (PKC) activation on cardiac mechanoenergetics is not fully understood. To address this issue, we determined the effects of the PKC activator phorbol 12-myristate 13-acetate (PMA) on isolated rat hearts. Hearts were exposed to PMA with or without pretreatment with the PKC inhibitor chelerythrine. Contractile efficiency was assessed as the reciprocal of the slope of the linear myocardial O2consumption (V˙o 2) pressure-volume area (PVA) relation. PMA decreased contractility ( E max; −30 ± 8%; P < 0.05) and increased coronary perfusion pressure (+58 ± 11%; P < 0.01) without altering left ventricular end-diastolic pressure. Concomitantly, PMA decreased PVA-independentV˙o 2 [nonmechanical energy expenditure for excitation-contraction (E-C) coupling and basal metabolism] by 28 ± 8% ( P < 0.05) and markedly increased contractile efficiency (+41 ± 8%; P < 0.05) in a manner independent of the coronary vascular resistance. Basal metabolism was not affected by PMA. Chelerythrine abolished the PMA-induced vasoconstriction, negative inotropy, decreased PVA-independent V˙o 2, and increased contractile efficiency. We conclude that PKC-mediated phosphorylation of regulatory proteins reduces V˙o 2 via effects on both the contractile machinery and the E-C coupling.

Endogenous endothelin-1 impairs endothelium-dependent relaxation after myocardial ischemia and reperfusion

1994 ◽  
Vol 267 (5) ◽  
pp. H1833-H1841 ◽  
Author(s):  
J. M. Hagar
Keyword(s):  
Myocardial Ischemia ◽  
Control Release ◽  
Microvascular Dysfunction ◽  
Coronary Perfusion Pressure ◽  
Left Ventricular ◽  
Coronary Perfusion ◽  
Ischemia And Reperfusion ◽  
Myocardial Ischemia And Reperfusion ◽  
Developed Pressure ◽  
Eta Receptor Antagonist

Endothelin (ET)-1 is produced in response to myocardial ischemia and reperfusion. It is a potent constrictor of coronary resistance vessels and may therefore contribute to myocardial injury and postischemic microvascular dysfunction. Isolated buffer-perfused rabbit hearts, under conditions of constant flow and isovolumic contraction, underwent 60 min of global ischemia and 60 min of reperfusion after pretreatment with selective ETA receptor antagonist BQ-123 (10(-7) M) in perfusate, exogenous ET-1 (10(-11) M), or control. Release of ET increased significantly at 20 and 60 min of reperfusion. BQ-123 did not enhance the recovery of left ventricular developed pressure or coronary perfusion pressure, whereas exogenous ET tended to worsen them. Cumulative creatine kinase release over 20 min of reperfusion did not differ significantly between groups. Maximum endothelium-dependent dilation to acetylcholine (ACh) was initially 62 +/- 6, 71 +/- 6, and 63 +/- 8% (SE) of U-46619-induced preconstriction in control, BQ-123-, and ET-treated hearts. At 20 min of reperfusion it was 37 +/- 5, 73 +/- 9, and 22 +/- 5%, and at 60 min of reperfusion it was 35 +/- 7, 79 +/- 6, and 22 +/- 3% (P < 0.001 for BQ-123 vs. control at 20 min and P < 0.0001 at 60 min). Endothelium-independent dilation to nitroglycerin was unaltered by ischemia and reperfusion. Neither BQ-123 alone nor a 1-h infusion of ET (10(-10) M) altered the response to ACh in nonischemic hearts.(ABSTRACT TRUNCATED AT 250 WORDS)

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